ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis-induced articular chondrocyte apoptosis and cytotoxicity.

Abstract

Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis. Our results revealed that acid (pH 6.0) decreased the cell viability and induced apoptosis of articular chondrocytes. PcTx1 and APETx2 combination significantly attenuated acidosis-induced chondrocyte cytotoxicity due to inhibit apoptosis, and this role could be enhanced by ASIC2a overexpression compared with the PcTx1 and APETx2 combination alone group. Moreover, both the [Ca2+]i levels and the levels of phosphorylated ERK1/2 as well as p38 were further reduced in acidosis-induced chondrocytes after ASIC2a overexpression in the presence of PcTx1 and APETx2. Furthermore, ASIC2a overexpression also reduced acid-induced the expression of ASIC1a. In addition, ASIC2a overexpression further promoted the PcTx1 and APETx2-increased levels of type II collagen in acidosis-induced chondrocytes. Taken together, the current data suggested that ASIC2a overexpression might enhance the anti-apoptotic and protective role of PcTx1 and APETx2 against acid-induced rat articular chondrocyte apoptosis by regulating ASIC1a expression and the [Ca2+]i levels and at least in part, suppressing p38 and ERK1/2 MAPK signaling pathways.

• Authors: Ren-Peng Zhou, Wen-Lin Ni, Bei-Bei Dai, Xiao-Shan Wu, Zhi-Sen Wang, Ya-Ya Xie, Zhi-Qiang Wang, Wei-Jie Yang, Jin-Fang Ge, Wei Hu, Fei-Hu Chen
• Journal: Gene (Gene) Vol. 642 Pg. 230-240 (Feb 05 2018) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 29141196 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• APETx2 protein, Anthopleura elegantissima
• ASIC2 protein, mouse
• Acid Sensing Ion Channel Blockers
• Acid Sensing Ion Channels
• Alkanesulfonic Acids
• Cnidarian Venoms
• Collagen Type II
• Morpholines
• PcTX1 protein, Psalmopoeus cambridgei
• Peptides
• Spider Venoms
• 2-(N-morpholino)ethanesulfonic acid

Topics

• Acid Sensing Ion Channel Blockers (pharmacology)
• Acid Sensing Ion Channels (genetics, metabolism)
• Acidosis (chemically induced, genetics, prevention & control)
• Alkanesulfonic Acids (adverse effects)
• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Chondrocytes (cytology, drug effects, metabolism)
• Cnidarian Venoms (pharmacology)
• Collagen Type II (metabolism)
• Drug Synergism
• Gene Expression Regulation (drug effects)
• Genetic Vectors (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Morpholines (adverse effects)
• Peptides (pharmacology)
• Plasmids (genetics)
• Rats
• Spider Venoms (pharmacology)